Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease

Celiac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or...

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Main Authors: Gloria Serena, Daniel Huynh, Rosiane S. Lima, Luciana M. Vise, Rachel Freire, Laura Ingano, Maureen M. Leonard, Stefania Senger, Alessio Fasano
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Nutrition
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnut.2019.00167/full
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author Gloria Serena
Gloria Serena
Daniel Huynh
Rosiane S. Lima
Luciana M. Vise
Rachel Freire
Rachel Freire
Laura Ingano
Maureen M. Leonard
Maureen M. Leonard
Stefania Senger
Stefania Senger
Alessio Fasano
Alessio Fasano
Alessio Fasano
spellingShingle Gloria Serena
Gloria Serena
Daniel Huynh
Rosiane S. Lima
Luciana M. Vise
Rachel Freire
Rachel Freire
Laura Ingano
Maureen M. Leonard
Maureen M. Leonard
Stefania Senger
Stefania Senger
Alessio Fasano
Alessio Fasano
Alessio Fasano
Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease
Frontiers in Nutrition
celiac disease
macrophages
epithelium
gliadin
innate immunity
author_facet Gloria Serena
Gloria Serena
Daniel Huynh
Rosiane S. Lima
Luciana M. Vise
Rachel Freire
Rachel Freire
Laura Ingano
Maureen M. Leonard
Maureen M. Leonard
Stefania Senger
Stefania Senger
Alessio Fasano
Alessio Fasano
Alessio Fasano
author_sort Gloria Serena
title Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease
title_short Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease
title_full Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease
title_fullStr Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease
title_full_unstemmed Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease
title_sort intestinal epithelium modulates macrophage response to gliadin in celiac disease
publisher Frontiers Media S.A.
series Frontiers in Nutrition
issn 2296-861X
publishDate 2019-11-01
description Celiac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or maintenance of the disease. Macrophages are extremely plastic immune cells that can be directed toward a pro- or anti-inflammatory phenotype by the surrounding microenvironment. Of note, gliadin, the most prominent causative agent of the disease, has been reported to trigger the production of pro-inflammatory cytokines in this cell population. In the present study, we aimed at investigating how the intestinal milieu and more specifically the epithelium can shape the macrophage response to gliadin. Using patient-derived organoids we showed that the intestinal epithelium derived from celiac disease donors releases anti-inflammatory factors that curb the macrophage response to gliadin. Furthermore, we uncovered that the celiac macrophages were better responders than macrophages derived from non-celiac controls. Finally, we demonstrated that IFNγ released by the epithelium is in part responsible of the observed anti-inflammatory effect. Our data shed light on the cross–talk between the immune system and the epithelium and its critical role in the intestinal homeostasis. Furthermore, we provide more evidence how alterations in the innate immune machinery in celiac patients may contribute to the onset of the disease.
topic celiac disease
macrophages
epithelium
gliadin
innate immunity
url https://www.frontiersin.org/article/10.3389/fnut.2019.00167/full
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spelling doaj-6c87e9951bfa4909b6e0e1496ea6d8a42020-11-25T01:36:17ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2019-11-01610.3389/fnut.2019.00167482289Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac DiseaseGloria Serena0Gloria Serena1Daniel Huynh2Rosiane S. Lima3Luciana M. Vise4Rachel Freire5Rachel Freire6Laura Ingano7Maureen M. Leonard8Maureen M. Leonard9Stefania Senger10Stefania Senger11Alessio Fasano12Alessio Fasano13Alessio Fasano14Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesEuropean Biomedical Research Institute of Salerno, Salerno, ItalyCeliac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or maintenance of the disease. Macrophages are extremely plastic immune cells that can be directed toward a pro- or anti-inflammatory phenotype by the surrounding microenvironment. Of note, gliadin, the most prominent causative agent of the disease, has been reported to trigger the production of pro-inflammatory cytokines in this cell population. In the present study, we aimed at investigating how the intestinal milieu and more specifically the epithelium can shape the macrophage response to gliadin. Using patient-derived organoids we showed that the intestinal epithelium derived from celiac disease donors releases anti-inflammatory factors that curb the macrophage response to gliadin. Furthermore, we uncovered that the celiac macrophages were better responders than macrophages derived from non-celiac controls. Finally, we demonstrated that IFNγ released by the epithelium is in part responsible of the observed anti-inflammatory effect. Our data shed light on the cross–talk between the immune system and the epithelium and its critical role in the intestinal homeostasis. Furthermore, we provide more evidence how alterations in the innate immune machinery in celiac patients may contribute to the onset of the disease.https://www.frontiersin.org/article/10.3389/fnut.2019.00167/fullceliac diseasemacrophagesepitheliumgliadininnate immunity